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Alpha-defensin as a diagnostic tool in revision total knee arthroplasties with unexpected positive intraoperative cultures and unexpected culture negative intraoperative cultures

  • Knee
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

Unexpected-positive-intraoperative-cultures (UPIC) are common in presumed aseptic revision-total-knee-arthroplasties (rTKA). However, the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, identification of an underlying pathogen was not possible, so-called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate the potential use of synovial alpha-defensin (AD) levels in these patients.

Methods

Synovial AD levels from 143 rTKAs were evaluated retrospectively from our prospectively maintained institutional periprostetic joint infection (PJI) biobank and database. The 2018-International Consensus Meeting (ICM) criteria was used to define the study groups. Samples from UPICs with a minimum of one positive intraoperative culture (ICM 2- ≥ 6) (n = 20) and UNIC’s (ICM ≥ 6) (n = 14) were compared to 34 septic culture-positive samples (ICM ≥ 6) and 75 aseptic culture-negative (ICM 0-1). Moreover, AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) in detecting the presence of AD in native and centrifuged synovial fluid specimens was performed. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were analysed.

Results

AD was positive in 31/34 (91.2%) samples from the septic culture-positive group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly associated with culture positive and histopathological results (p < 0.001). No high-virulent microorganisms (0/20) were present in the UPIC group, compared to infected-group (19/34; 55.9%). High virulent microorganisms showed a positive AD result in 89.5% (17/19) of the cases. Methicillin resistant Staphylococcus epidermis (MRSE) infections had significantly higher AD levels than with methicillin susceptible S. epidermdis (MSSE) (p = 0.003). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid.

Conclusion

AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnosis of UPIC and UNIC associated to rTKAs. Pathogen virulence as well as antibiotic resistance pattern may have an effect on AD levels. Centrifugation of synovial fluid had no influence on ADLF results.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AD:

Alpha defensin

ADLF:

Alpha-defensin-lateral-flow-assay

BMI:

Body mass index

CoNS:

Coagulase-negative Staphylococci

CRP:

C-reactive protein

DAIR:

Debridement-antibiotics and implant retention

ELISA:

Enzyme-linked immunosorbent assay

EUCAST:

European Committee on Antimicrobial Susceptibility Testing

ICM:

2018-International Consensus Meeting

M:

Mean

Md:

Median

MRSA:

Methicillin-resistant Staphylococcus aureus

MRSE:

Methicillin-resistant Staphylococcus epidermidis

MSSA:

Methicillin-susceptible Staphylococcus aureus

MSSE:

Methicillin-susceptible Staphylococcus epidermidis

PJI:

Periprosthetic joint infection

PMN:

Polymorphonuclear percentage

rTKA:

Revision total knee arthroplasty

SD:

Standard deviation

SLIM:

Synovial-like interface membrane

TKA:

Total knee arthroplasty

UNIC:

Unexpected negative intraoperative cultures

UPIC:

Unexpected positive intraoperative cultures

*:

p < 0.05

**:

p < 0.001

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Authors and Affiliations

  1. Michael Ogon Laboratory for Orthopaedic Research, Orthopaedic Hospital Vienna-Speising, Speisinger Straße 109, Vienna, Austria

    Sebastian Simon, Bernhard J. H. Frank, Alexander Aichmair, Jennyfer A. Mitterer, Susana Gardete Hartmann & Jochen G. Hofstaetter

  2. II. Department of Orthopaedic Surgery, Orthopaedic Hospital Vienna-Speising, Speisinger Straße 109, Vienna, Austria

    Sebastian Simon, Alexander Aichmair, Martin Dominkus, Michael Kasparek & Jochen G. Hofstaetter

  3. School of Medicine, Sigmund Freud University Vienna, Freudplatz1+3, Vienna, Austria

    Martin Dominkus

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Contributions

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data: SS, BJHF, AA, MD, MK, JAM, SGH; JGH. Have been involved in drafting the manuscript or revising it critically for important intellectual content SS, BJHF, AA, MD, MK, JAM, SGH, JGH. Have given final approval of the version to be published SS, BJHF, AA, MD, MK, JAM, SGH, JGH. Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SS, BJHF, AA, MD, MK, JAM, SGH, JGH.

Corresponding author

Correspondence to Jochen G. Hofstaetter.

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Conflict of interest

The institution of one or more of the authors (S.S., B.J.H.F., A.A., M.D., M.K., J.A.M., S.G.H; J.G.H.) has received funding from Zimmer Biomet. Zimmer Biomet covered the costs of Synovasure® Alpha Defensin Lateral Flow and Synovasure® Alpha Defensin ELISA Laboratory Test.

Ethical approval

A retrospective analysis from synovial fluid samples of revision and re-revision TKAs of our prospectively collected biobank (2016–2021) was performed.

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The authors certify that they do not have affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject or materials discussed in this manuscript.

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Simon, S., Frank, B.J.H., Aichmair, A. et al. Alpha-defensin as a diagnostic tool in revision total knee arthroplasties with unexpected positive intraoperative cultures and unexpected culture negative intraoperative cultures. Knee Surg Sports Traumatol Arthrosc 31, 1462–1469 (2023). https://doi.org/10.1007/s00167-022-07268-w

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